Many chronic pain disorders are more prevalent in women. Women also exhibit greater sensitivity to experimentally induced pain. Research has suggested that sex hormones exert multiple impacts upon human CNS, including the sympathoadrenal and serotonergic functions. The primary purpose of this proposal is to test several components of a conceptual model hypothesizing how the hormonal and stress factors are related to fibromyalgia syndrome (FMS), a chronic musculoskeletal pain disorder, predominantly seen in women. We will use both laboratory and field study approaches to evaluate the effects of sex hormones in pain sensitivity, stress reactivity, and symptom perception across a menstrual cycle in women with FMS, in comparisons to healthy pain-free females (PFF) and males (PFM). Specifically, we will test sex steroid production in FMS, estrogenic effects on the sympathoadrenal functions in response to stressors, estrogenic effects on pain sensitivity, involvement of sex hormones in perimenstrual and FMS symptoms across menstrual cycle, and sleep and stress as predictors of pain, fatigue, distressed mood in FMS. A total of 300 subjects (100 each in FMS, PFF, PFM) will undergo home urine tests, daily symptom monitoring, blood and saliva sampling, and experimentally induced stress and pain testing. The laboratory testing will be repeated on 3 separate days: once during the mid-luteal phase (high estrogen E + high progesterone P), once during the perimenstrual phase (low E + low P), and once during the late-follicular phase (high E + low P). Male subjects will be scheduled using a "yoked-cycle" to female subjects. Each subject will be randomly assigned to one of the two experimental conditions ("stress-priming" vs "non-stress- priming" tasks just prior to pain testing). Blood pressure and salivary cortisol will be sampled multiple times throughout the laboratory sessions. The findings from this project are expected to promote better understanding of the role of female sex hormones in noxious sensory processing in chronic pain disorders.